BACKGROUND: The Phase 2 SCALOP trial compared gemcitabine with capecitabine-based consolidation chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC). METHODS: Thirty-five systematically identified circulating biomarkers were analysed in plasma samples from 60 patients enroled in SCALOP. Each was measured in triplicate at baseline (prior to three cycles of gemcitabine-capecitabine induction chemotherapy) and, for a subset, prior to CRT. Association with overall survival (OS) was determined using univariable Cox regression and optimal thresholds delineating low to high values identified using time-dependent ROC curves. Independence from known prognostic factors was assessed using Spearman correlation and the Wilcoxon rank sum test prior to multivariable Cox regression modelling including independent biomarkers and known prognostic factors. RESULTS: Baseline circulating levels of C-C motif chemokine ligand 5 (CCL5) were significantly associated with OS, independent of other clinicopathological characteristics. Patients with low circulating CCL5 (CCL5low) had a median OS of 18.5 (95% CI 11.76-21.32) months compared to 11.3 (95% CI 9.86-15.51) months in CCL5high; hazard ratio 1.95 (95% CI 1.04-8.65; p = 0.037). CONCLUSIONS: CCL5 is an independent prognostic biomarker in LAPC. Given the known role of CCL5 in tumour invasion, metastasis and the induction of an immunosuppressive micro-environment, targeting of CCL5-mediated pathways may offer therapeutic potential in pancreatic cancer. CLINICAL TRIAL REGISTRATION: The SCALOP trial was registered with ISRCTN, number 96169987 (registered 29 May 2008).
BACKGROUND: The Phase 2 SCALOP trial compared gemcitabine with capecitabine-based consolidation chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC). METHODS: Thirty-five systematically identified circulating biomarkers were analysed in plasma samples from 60 patients enroled in SCALOP. Each was measured in triplicate at baseline (prior to three cycles of gemcitabine-capecitabine induction chemotherapy) and, for a subset, prior to CRT. Association with overall survival (OS) was determined using univariable Cox regression and optimal thresholds delineating low to high values identified using time-dependent ROC curves. Independence from known prognostic factors was assessed using Spearman correlation and the Wilcoxon rank sum test prior to multivariable Cox regression modelling including independent biomarkers and known prognostic factors. RESULTS: Baseline circulating levels of C-C motif chemokine ligand 5 (CCL5) were significantly associated with OS, independent of other clinicopathological characteristics. Patients with low circulating CCL5 (CCL5low) had a median OS of 18.5 (95% CI 11.76-21.32) months compared to 11.3 (95% CI 9.86-15.51) months in CCL5high; hazard ratio 1.95 (95% CI 1.04-8.65; p = 0.037). CONCLUSIONS: CCL5 is an independent prognostic biomarker in LAPC. Given the known role of CCL5 in tumour invasion, metastasis and the induction of an immunosuppressive micro-environment, targeting of CCL5-mediated pathways may offer therapeutic potential in pancreatic cancer. CLINICAL TRIAL REGISTRATION: The SCALOP trial was registered with ISRCTN, number 96169987 (registered 29 May 2008).
Authors: Talia Golan; Pascal Hammel; Michele Reni; Eric Van Cutsem; Teresa Macarulla; Michael J Hall; Joon-Oh Park; Daniel Hochhauser; Dirk Arnold; Do-Youn Oh; Anke Reinacher-Schick; Giampaolo Tortora; Hana Algül; Eileen M O'Reilly; David McGuinness; Karen Y Cui; Katia Schlienger; Gershon Y Locker; Hedy L Kindler Journal: N Engl J Med Date: 2019-06-02 Impact factor: 91.245
Authors: Carolina Torres; Ana Linares; Maria José Alejandre; Rogelio J Palomino-Morales; Octavio Caba; Jose Prados; Antonia Aránega; Juan R Delgado; Antonio Irigoyen; Joaquina Martínez-Galán; Francisco M Ortuño; Ignacio Rojas; Sonia Perales Journal: Biomed Res Int Date: 2015-08-04 Impact factor: 3.411
Authors: Fleur van der Sijde; Willem A Dik; Dana A M Mustafa; Eveline E Vietsch; Marc G Besselink; Reno Debets; Bas Groot Koerkamp; Brigitte C M Haberkorn; Marjolein Y V Homs; Quisette P Janssen; Saskia A C Luelmo; Leonie J M Mekenkamp; Astrid A M Oostvogels; Marja A W Smits-Te Nijenhuis; Johanna W Wilmink; Casper H J van Eijck Journal: Front Immunol Date: 2022-08-25 Impact factor: 8.786